Nobiletin Protects from Renal Ischemia-Reperfusion Injury in Rats by Suppressing Inflammatory Cytokines and Regulating iNOS-eNOS Expressions

Güvenç, Mehmet; Cellat, Mustafa; Uyar, Ahmet; Özkan, Hüseyin; Gökçek, İ̇shak; İşler, Cafer Tayer; Yakan, Akın

doi:10.1007/s10753-019-01123-w

Cited by 24 publications

(15 citation statements)

References 51 publications

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“…Another pathological condition that can be alleviated by NOB is ischemic/reperfusion (I/R) injury, a condition involved in enhancing oxidative stress and inflammation [76]. Notably, NOB dually enhances the activity of antioxidant enzymes such as catalase and glutathione peroxidase (GSH-PX), whereas it diminishes the concentration of IL-6 and TNF-α, leading to amelioration of I/R-mediated inflammation and oxidative stress [77]. It has been demonstrated that antioxidant and anti-inflammatory activities of NOB during I/R is mediated by mitogen-activated protein kinase (MAPK) induction [78].…”

Section: Therapeutic and Biological Activities Of Nobmentioning

confidence: 99%

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways

et al. 2020

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Cancer therapy is a growing field, and annually, a high number of research is performed to develop novel antitumor drugs. Attempts to find new antitumor drugs continue, since cancer cells are able to acquire resistance to conventional drugs. Natural chemicals can be considered as promising candidates in the field of cancer therapy due to their multiple-targeting capability. The nobiletin (NOB) is a ubiquitous flavone isolated from Citrus fruits. The NOB has a variety of pharmacological activities, such as antidiabetes, antioxidant, anti-inflammatory, hepatoprotective, and neuroprotective. Among them, the antitumor activity of NOB has been under attention over recent years. In this review, we comprehensively describe the efficacy of NOB in cancer therapy. NOB induces apoptosis and cell cycle arrest in cancer cells. It can suppress migration and invasion of cancer cells via the inhibition of epithelial-to-mesenchymal transition (EMT) and EMT-related factors such as TGF-β, ZEB, Slug, and Snail. Besides, NOB inhibits oncogene factors such as STAT3, NF-κB, Akt, PI3K, Wnt, and so on. Noteworthy, onco-suppressor factors such as microRNA-7 and -200b undergo upregulation by NOB in cancer therapy. These onco-suppressor and oncogene pathways and mechanisms are discussed in this review.

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Section: Therapeutic and Biological Activities Of Nobmentioning

confidence: 99%

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways

et al. 2020

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“…[5][6][7] In the past few years, the protective effects of Nobiletin against ischemic injury were reported in hepatic, renal, and cerebral ischemic diseases. [8][9][10] Studies have shown that Nobiletin could alleviate hippocampal injury following cerebral ischemia and improve learning and memory. [11][12][13] While there are few studies of Nobiletin on myocardial infarction, our previous study found that Nobiletin could protect against myocardial ischemic injury through restoration of autophagic flux, alleviation of apoptosis, and reduction in cardiac remodeling.…”

Section: Introductionmentioning

confidence: 99%

“…Nobiletin is a polymethoxy flavonoid enriched in citrus, which was reported to have anti‐inflammatory, 5,6 anticancer, 7 and antiapoptotic effects 5–7 . In the past few years, the protective effects of Nobiletin against ischemic injury were reported in hepatic, renal, and cerebral ischemic diseases 8–10 . Studies have shown that Nobiletin could alleviate hippocampal injury following cerebral ischemia and improve learning and memory 11–13 .…”

Section: Introductionmentioning

confidence: 99%

Nobiletin ameliorates cardiac impairment and alleviates cardiac remodeling after acute myocardial infarction in rats via JNK regulation

Liu

Gao

Zeng

et al. 2021

Pharmacology Res & Perspec

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Nobiletin was found to protect against acute myocardial infarction (AMI)‐induced cardiac function decline and myocardial remodeling, although the dose–effect relationship and underlying pathways remained unclear. In the current research, different doses of Nobiletin (7.5, 15 and 30 mg/kg/day) were administered to AMI rat model for 21 days. Survival rate, echocardiography, and histological analysis were assessed in vivo. In addition, MTT assay, flow cytometry, and Western blotting were conducted to explore Nobiletin's cytotoxicity and antiapoptotic effect on H9C2 cells. Mechanistically, the activation of MAPK effectors and p38 in vivo was studied. The results showed medium‐ and high‐dose Nobiletin could significantly improve survival rate and cardiac function and reduce the area of infarction and cardiac fibrosis. Medium dose showed the best protection on cardiac functions, whereas high dose showed the best protective effect on cellular apoptosis and histological changes. JNK activation was significantly inhibited by Nobiletin in vivo, which could help to explain the partial contribution of autophagy to AMI‐induced apoptosis and the discrepancy on dose–effect relationships. Together, our study suggested that JNK inhibition plays an important role in Nobiletin‐induced antiapoptotic effect in myocardial infarction, and medium‐dose Nobiletin demonstrated the strongest effect in vivo.

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“…Nobiletin, a polymethoxy flavonoid, has been proven to exert multiple beneficial activities, including anticarcinogenic, anti-inflammatory, antiasthmatic, and neuroprotective effects [ 28 ]. A recent study showed that nobiletin protects against ischemia-reperfusion injury by attenuating oxidative stress and inflammation [ 29 ]. Hesperetin, a member of the flavanone class of flavonoids, has been widely studied for its anticancer, antioxidant, and anti-inflammatory properties [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Systematically Deciphering the Pharmacological Mechanism of Fructus Aurantii via Network Pharmacology

Jin

Gao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Fructus Aurantii (FA) is a traditional herbal medicine that has been widely used for thousands of years in China and possesses a variety of pharmacological effects. However, the active ingredients in FA and the potential mechanisms of its therapeutic effects have not been fully explored. Here, we applied a network pharmacology approach to explore the potential mechanisms of FA. We identified 5 active compounds from FA and a total of 209 potential targets to construct a protein-protein interaction (PPI) network. Prostaglandin G/H synthase 2 (PTGS2), heat shock protein 90 (HSP90), cell division protein kinase 6 (CDK6), caspase 3 (CASP3), apoptosis regulator Bcl-2 (Bcl-2), and matrix metalloproteinase-9 (MMP9) were identified as key targets of FA in the treatment of multiple diseases. Gene ontology (GO) enrichment demonstrated that FA was highly related to transcription initiation from RNA polymerase II promoter, DNA-templated transcription, positive regulation of transcription, regulation of apoptosis process, and regulation of cell proliferation. Various signaling pathways involved in the treatment of FA were identified, including pathways in cancer and pathways specifically related to prostate cancer, colorectal cancer, PI3K-Akt, apoptosis, and non-small-cell lung cancer. TP53, AKT1, caspase 3, MAPK3, PTGS2, and BAX/BCL2 were related key targets in the identified enriched pathways and the PPI network. In addition, our molecular docking results showed that the bioactive compounds in FA can tightly bind to most target proteins. This article reveals via network pharmacology research the possible mechanism(s) by which FA exerts its activities in the treatment of various diseases and lays a foundation for further experiments and the development of a rational clinical application of FA.

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Nobiletin Protects from Renal Ischemia-Reperfusion Injury in Rats by Suppressing Inflammatory Cytokines and Regulating iNOS-eNOS Expressions

Cited by 24 publications

References 51 publications

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways

Nobiletin ameliorates cardiac impairment and alleviates cardiac remodeling after acute myocardial infarction in rats via JNK regulation

Systematically Deciphering the Pharmacological Mechanism of Fructus Aurantii via Network Pharmacology

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